Restoration and HDX-MS Epitope Mapping of a Broad-Spectrum SARS-Cov-2 Antibody

Highly contagious diseases like SARS-Cov-2 posts a major threat for public health and global economy, both preventative and therapeutic solutions are therefore urgently needed. Through the use of epitope-guided antibody design, we successfully restored a broad-spectrum SARS-Cov therapeutic antibody for SARS-Cov-2. Compared to the precursor antibody CR3022, the new antibody NOVOAB-20 binds to SARS-Cov-2 receptor binding domain (RBD) with a more than 10-fold higher affinity. Its binding site on RBD was determined at amino acid resolution using an enhanced HDX-MS epitope mapping technology. Because this antibody targets a highly conserved epitope similar to CR3022 and the mutations on SARS-Cov-2 known so far are all not in this region, it also has the potential to block future SARS-Cov-2 mutants. As a fully humanized antibody, NOVOAB-20 is a promising candidate to be developed as potential therapeutics for SARS-Cov-2, either as monotherapy or in combination with other neutralizing antibodies targeting different epitopes (e.g. the ACE2 binding site).